Asymmetric Subthalamic Deep Brain Stimulation for Axial Motor Dysfunction in Parkinson's Disease

NCT03462082 | Completed Results DMC

• 1 other identifier: 17-5785
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This single-center, randomized, quadruple-blinded, double-crossover comparative efficacy trial will study the effects of unilateral 50% voltage reduction in axial motor dysfunction for patients with Parkinson's disease that develop treatment-resistant postural stability gait dysfunction after bilateral subthalamic nucleus deep brain stimulation surgery.

Conditions

Parkinson Disease

Keywords

Parkinson's disease; axial motor dysfunction; asymmetric neuromodulation; subthalamic nucleus deep brain stimulation

Outcome Measures

Primary Outcomes (1)

• Change in Gait Velocity

  As measured during the 10-meter walk test. In this test, participants walk at their usual, regular pace over a total distance of 10 meters. The middle 6-meters (between the 2-meter and 8-meter marks) are timed to measure gait velocity during steady-state gait.

  Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)

Secondary Outcomes (13)

• Change in Motor Function

  Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)

• Change in Axial Motor Function (1)

  Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)

• Change in Axial Motor Function (2)

  Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)

• Change in Axial Motor Function (3)

  Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)

• Change in Quantitative Gait Analysis (1)

  Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)

Study Arms (3)

Baseline STN-DBS

NO INTERVENTION

Maintenance of baseline bilateral STN-DBS settings.

Asymmetric STN-DBS 1

EXPERIMENTAL

Unilateral 50% reduction of voltage (e.g. right side)

Other: Asymmetric STN-DBS

Asymmetric STN-DBS 2

EXPERIMENTAL

Unilateral 50% reduction of voltage (e.g. left side)

Other: Asymmetric STN-DBS

Interventions

Asymmetric STN-DBS OTHER

Asymmetric deep brain stimulation

Asymmetric STN-DBS 1; Asymmetric STN-DBS 2

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with Parkinson's disease (PD) (previously diagnosed according to the UK brain bank criteria) who develop treatment-resistant postural instability gait dysfunction (PIGD) more than 6 months but less than 5 years after bilateral subthalamic nucleus deep brain stimulation (STN-DBS).
• Treatment-resistant PIGD will be defined as freezing of gait and UPDRS or MDS-UPDRS PIGD subscales of more than 6 points despite optimization of medications and bilateral STN-DBS programming.

You may not qualify if:

• Treatment-resistant PIGD less than 6 months or more than 5 years after STN-DBS surgery.
• PIGD responsive to optimization of medications and/or bilateral STN-DBS programming.
• Cognitive impairment or psychiatric comorbidities (including substance abuse) that would interfere with the informed consent process, study adherence or outcome assessments.
• Advanced PD or any other neurological, cardiovascular or musculoskeletal co-morbidities that would preclude or require assistance to complete the 10-meter walking test.
• Patients not able to comply with 4-week interval evaluations following their potential enrollment due to personal reasons.
• Serious illness (requiring systemic treatment and/or hospitalization) until subject either completes therapy or is clinically-stable on therapy, in the opinion of the site investigator, for at least 30 days prior to study entry.
• Inability or unwillingness of subject or legal guardian/representative to give written informed consent.

Sponsors & Collaborators

• University of Toronto: lead

Study Sites (1)

Movement disorders Centre, Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

Related Publications (4)

• Fasano A, Herzog J, Seifert E, Stolze H, Falk D, Reese R, Volkmann J, Deuschl G. Modulation of gait coordination by subthalamic stimulation improves freezing of gait. Mov Disord. 2011 Apr;26(5):844-51. doi: 10.1002/mds.23583. Epub 2011 Mar 2.

  PMID: 21370271 BACKGROUND

• Lizarraga KJ, Jagid JR, Luca CC. Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation on gait kinematics in Parkinson's disease: a randomized, blinded study. J Neurol. 2016 Aug;263(8):1652-6. doi: 10.1007/s00415-016-8191-3. Epub 2016 Jun 8.

  PMID: 27278062 BACKGROUND

• Lizarraga KJ, Luca CC, De Salles A, Gorgulho A, Lang AE, Fasano A. Asymmetric neuromodulation of motor circuits in Parkinson's disease: The role of subthalamic deep brain stimulation. Surg Neurol Int. 2017 Oct 24;8:261. doi: 10.4103/sni.sni_292_17. eCollection 2017.

  PMID: 29184712 BACKGROUND

• Lizarraga KJ, Gnanamanogaran B, Al-Ozzi TM, Cohn M, Tomlinson G, Boutet A, Elias GJB, Germann J, Soh D, Kalia SK, Hodaie M, Munhoz RP, Marras C, Hutchison WD, Lozano AM, Lang AE, Fasano A. Lateralized Subthalamic Stimulation for Axial Dysfunction in Parkinson's Disease: A Randomized Trial. Mov Disord. 2022 May;37(5):1079-1087. doi: 10.1002/mds.28953. Epub 2022 Feb 13.

  PMID: 35156734 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Limitations and Caveats

There were no dropouts. The study phase of the trial concluded after the 22nd patient completed participation. As established by the sample size calculation, the originally planned enrollment of 27 patients was not necessary.

Results Point of Contact

• Title: Karlo J Lizarraga, MD, MS / Assistant Professor of Neurology
• Organization: University of Rochester

karlo.lizarraga@gmail.com

585-341-7500

Study Officials

• Alfonso Fasano, MD, PhD

  University of Toronto

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 5, 2018
• First Posted: March 12, 2018
• Study Start: March 14, 2018
• Primary Completion: April 15, 2019
• Study Completion: April 15, 2019
• Last Updated: January 5, 2021
• Results First Posted: January 5, 2021

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: To be shared as supplementary data upon publication of the results of the trial.

Locations

CA (1)